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NCT Number: NCT04251026

A Study of Tividenofusp Alfa (DNL310) in Pediatric Participants With Hunter Syndrome

This is a multicenter, multiregional, open-label study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme replacement therapy (ERT), designed to treat both the peripheral and CNS manifestations of Mucopolysaccharidosis type II (MPS II; Hunter syndrome).

Participants, whose physicians feel they are deriving benefit, will have the opportunity to be reconsented into a safety extension and then an open-label extension for continued evaluation.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Mucopolysaccharidosis II Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Death Death, Sudden Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Infant Death Intellectual Disability Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Skin and Connective Tissue Diseases Sudden Infant Death X-Linked Intellectual Disability

Age range

Up to 18 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

McGill University Health Centre - Royal Victoria Hospital, Montreal, Quebec, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Confirmed diagnosis of MPS II
  • Cohort A: Participants aged ≥5 to ≤10 years with neuronopathic MPS II
  • Cohort B: Participants aged ≥1 to ≤18 years with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype
  • Cohort C: Participants aged <4 years with neuronopathic MPS II (this cohort can include participants ≥4 to ≤18 years of age if participant is a blood relative of a participant <4 years of age)
  • Cohort D: Participants aged ≤18 years with non-neuronopathic MPS II or neuronopathic MPS II with preexisting hepatomegaly who have never taken standard-of-care ERT
  • Cohort E: neuronopathic MPS II participants aged ≥6 years at screening, non-neuronopathic MPS II participants <6 or ≥17 years at screening, and neuronopathic MPS II participants ≥1 to ≤18 years at screening with a history of prior haematopoietic stem cell transplantation or gene therapy who have completed at least 48 weeks in Study DNLI-E-0001
  • For participants receiving intravenous iduronate 2-sulfatase (IDS) ERT, tolerated a minimum of 4 months of therapy during the period immediately prior to screening.

Key Exclusion Criteria:

  • Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
  • Use of any CNS-targeted MPS II ERT within 3 months before study start for participants aged ≥5 years, and within 6 months before study start for participants aged <5 years
  • Use of IDS gene therapy or stem cell therapy at any time (except for participants in Cohort E)
  • Clinically significant thrombocytopenia, other clinically significant coagulation abnormality, or significant active bleeding, or required treatment with an anticoagulant or more than two antiplatelet agents
  • Contraindication for lumbar punctures
  • Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any CNS disease that is not MPS II-related within 1 year of screening
  • Have had a ventriculoperitoneal (VP) shunt placed, or any other brain surgery, or have a clinically significant VP shunt malfunction within 30 days of screening
  • Have any clinically significant CNS trauma or disorder that, in the opinion of the investigator, may interfere with assessment of study endpoints or make participation in the study unsafe

Treatment and study plan

tividenofusp alfa

Drug

Intravenous repeating dose

Primary outcomes

  1. Incidence and severity of treatment-emergent adverse events (TEAEs)

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  2. Change from baseline in urine total glycosaminoglycan (GAG) concentrations

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  3. Incidence and severity of infusion-related reactions (IRRs)

    Time frame: 24 weeks, 104 weeks, and 357 weeks

  4. Change from baseline in concomitant medications

    Time frame: 24 weeks, 104 weeks, and 357 weeks

Secondary outcomes

  1. Percentage change from baseline in cerebrospinal fluid (CSF) of heparan sulfate

    Time frame: 24 weeks

  2. Participants with improvement in individual disease progression in the Vineland Adaptive Behavior Scale Adaptive Behavior Composite (ABC) score

    Time frame: 49 weeks

  3. Participants with improvement in individual disease progression in the Vineland Adaptive Behavior Scale subdomain scores

    Time frame: 49 weeks

  4. PK parameter: Maximum observed concentration (Cmax) of DNL310 in serum

    Time frame: 24 weeks

  5. PK parameter: Trough concentration (Cmin) of DNL310 in serum

    Time frame: 24 weeks

  6. PK parameter: Time to maximum observed concentration (tmax) of DNL310 in serum

    Time frame: 24 weeks

  7. PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of DNL310 in serum

    Time frame: 24 weeks

  8. PK parameter: Area under the concentration-time curve from time zero to infinity (AUC∞) of DNL310 in serum

    Time frame: 24 weeks

  9. PK parameter: Area under the concentration-time curve over a dosing interval (AUCτ) of DNL310 in serum

    Time frame: 24 weeks

  10. PK parameter: Apparent terminal elimination half-life (t½) of DNL310 in serum

    Time frame: 24 weeks

  11. Characterization of immunogenicity of DNL310 in serum, as measured by the incidence of anti-drug antibodies (ADAs) relative to baseline

    Time frame: 24 weeks

  12. Percent change from baseline in urine concentration of heparan sulfate (HS)

    Time frame: 24 weeks

  13. Participants with liver volume in the normal range

    Time frame: 24 weeks and 49 weeks

  14. Percentage change from baseline in liver volume

    Time frame: 24 weeks and 49 weeks

Sponsors and collaborators

Lead sponsor

Denali Therapeutics Inc.

Industry

Registry information

Official study title

A Phase 1/2, Multicenter, Open-Label Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants With Hunter Syndrome

Important dates

Study start
2020
Primary completion
2031
Study completion
2031
First posted
Jan 31, 2020
Registry last updated
Aug 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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